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At least 1,351 records · Page 75

Modeling resistance to the broadly neutralizing antibody PGT121 in people living with HIV-1

PGT121 is a broadly neutralizing antibody in clinical development for the treatment and prevention of HIV-1 infection via passive administration. PGT121 targets the HIV-1 V3-glycan and demonstrated potent antiviral activity in a phase I clinical trial. Resistance to PGT121 monotherapy rapidly occurred in the majority of participants in this trial with the sampled rebound viruses being entirely resistant to PGT121 mediated neutralization. However, two individuals experienced long-term ART-free viral suppression following antibody infusion and retained sensitivity to PGT121 upon viral rebound. Here, we develop mathematical models of the HIV-1 dynamics during this phase I clinical trial. We utilize these models to understand the dynamics leading to PGT121 resistance and to identify the mechanisms driving the observed long-term viral control. Our modeling highlights the importance of the relative fitness difference between PGT121 sensitive and resistant subpopulations prior to treatment. Specifically, by fitting our models to data, we identify the treatment-induced competitive advantage of previously existing or newly generated resistant population as a primary driver of resistance. Finally, our modeling emphasizes the high neutralization ability of PGT121 in both participants who exhibited long-term viral control.

60 APPLIED LIFE SCIENCES↗

A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B

Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound frequently occurs following treatment interruption. Consequently, functional cure rates of chronic HBV infection remain low and there is increased interest in a novel treatment modality, capsid assembly modulators (CAMs). Here, we develop a multiscale mathematical model of CAM treatment in chronic HBV infection. By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug’s dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection. Finally, we demonstrate analytically and numerically that the relative change of HBV RNA more accurately reflects the antiviral effectiveness of a CAM than the relative change in HBV DNA.

59 BASIC BIOLOGICAL SCIENCES↗

Zinc against COVID-19? Symptom surveillance and deficiency risk groups

A wide variety of symptoms is associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, and these symptoms can overlap with other conditions and diseases. Knowing the distribution of symptoms across diseases and individuals can support clinical actions on timelines shorter than those for drug and vaccine development. Here, we focus on zinc deficiency symptoms, symptom overlap with other conditions, as well as zinc effects on immune health and mechanistic zinc deficiency risk groups. There are well-studied beneficial effects of zinc on the immune system including a decreased susceptibility to and improved clinical outcomes for infectious pathogens including multiple viruses. Zinc is also an anti-inflammatory and anti-oxidative stress agent, relevant to some severe Coronavirus Disease 2019 (COVID-19) symptoms. Unfortunately, zinc deficiency is common worldwide and not exclusive to the developing world. Lifestyle choices and preexisting conditions alone can result in zinc deficiency, and we compile zinc risk groups based on a review of the literature. It is also important to distinguish chronic zinc deficiency from deficiency acquired upon viral infection and immune response and their different supplementation strategies. Zinc is being considered as prophylactic or adjunct therapy for COVID-19, with 12 clinical trials underway, highlighting the relevance of this trace element for global pandemics. Using the example of zinc, we show that there is a critical need for a deeper understanding of essential trace elements in human health, and the resulting deficiency symptoms and their overlap with other conditions. This knowledge will directly support human immune health for decreasing susceptibility, shortening illness duration, and preventing progression to severe cases in the current and future pandemics.

59 BASIC BIOLOGICAL SCIENCES↗

Using heterogeneous data to identify signatures of dengue outbreaks at fine spatio-temporal scales across Brazil

Dengue virus remains a significant public health challenge in Brazil, and seasonal preparation efforts are hindered by variable intra- and interseasonal dynamics. Here, we present a framework for characterizing weekly dengue activity at the Brazilian mesoregion level from 2010–2016 as time series properties that are relevant to forecasting efforts, focusing on outbreak shape, seasonal timing, and pairwise correlations in magnitude and onset. In addition, we use a combination of 18 satellite remote sensing imagery, weather, clinical, mobility, and census data streams and regression methods to identify a parsimonious set of covariates that explain each time series property. The models explained 54% of the variation in outbreak shape, 38% of seasonal onset, 34% of pairwise correlation in outbreak timing, and 11% of pairwise correlation in outbreak magnitude. Regions that have experienced longer periods of drought sensitivity, as captured by the “normalized burn ratio,” experienced less intense outbreaks, while regions with regular fluctuations in relative humidity had less regular seasonal outbreaks. Both the pairwise correlations in outbreak timing and outbreak trend between mesoresgions were best predicted by distance. Our analysis also revealed the presence of distinct geographic clusters where dengue properties tend to be spatially correlated. Forecasting models aimed at predicting the dynamics of dengue activity need to identify the most salient variables capable of contributing to accurate predictions. Our findings show that successful models may need to leverage distinct variables in different locations and be catered to a specific task, such as predicting outbreak magnitude or timing characteristics, to be useful. This advocates in favor of “adaptive models” rather than “one-size-fits-all” models. The results of this study can be applied to improving spatial hierarchical or target-focused forecasting models of dengue activity across Brazil.

59 BASIC BIOLOGICAL SCIENCES↗

People who inject drugs in metropolitan Chicago: A meta-analysis of data from 1997-2017 to inform interventions and computational modeling toward hepatitis C microelimination

Progress toward hepatitis C virus (HCV) elimination in the United States is not on track to meet targets set by the World Health Organization, as the opioid crisis continues to drive both injection drug use and increasing HCV incidence. A pragmatic approach to achieving this is using a microelimination approach of focusing on high-risk populations such as people who inject drugs (PWID). Computational models are useful in understanding the complex interplay of individual, social, and structural level factors that might alter HCV incidence, prevalence, transmission, and treatment uptake to achieve HCV microelimination. However, these models need to be informed with realistic sociodemographic, risk behavior and network estimates on PWID. We conducted a meta-analysis of research studies spanning 20 years of research and interventions with PWID in metropolitan Chicago to produce parameters for a synthetic population for realistic computational models (e.g., agent-based models). We then fit an exponential random graph model (ERGM) using the network estimates from the meta-analysis in order to develop the network component of the synthetic population.

60 APPLIED LIFE SCIENCES↗

Modeling hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and mortality worldwide. Direct-acting antiviral (DAA) therapy leads to high cure rates. However, persons who inject drugs (PWID) are at risk for reinfection after cure and may require multiple DAA treatments to reach the World Health Organization’s (WHO) goal of HCV elimination by 2030. Using an agent-based model (ABM) that accounts for the complex interplay of demographic factors, risk behaviors, social networks, and geographic location for HCV transmission among PWID, we examined the combination(s) of DAA enrollment (2.5%, 5%, 7.5%, 10%), adherence (60%, 70%, 80%, 90%) and frequency of DAA treatment courses needed to achieve the WHO’s goal of reducing incident chronic infections by 90% by 2030 among a large population of PWID from Chicago, IL and surrounding suburbs. We also estimated the economic DAA costs associated with each scenario. Our results indicate that a DAA treatment rate of >7.5% per year with 90% adherence results in 75% of enrolled PWID requiring only a single DAA course; however 19% would require 2 courses, 5%, 3 courses and <2%, 4 courses, with an overall DAA cost of $325 million to achieve the WHO goal in metropolitan Chicago. We estimate a 28% increase in the overall DAA cost under low adherence (70%) compared to high adherence (90%). Our modeling results have important public health implications for HCV elimination among U.S. PWID. Using a range of feasible treatment enrollment and adherence rates, we report robust findings supporting the need to address re-exposure and reinfection among PWID to reduce HCV incidence.

60 APPLIED LIFE SCIENCES↗

Incidence and predictors of tuberculosis among children receiving antiretroviral therapy in the Wolaita Zone: A retrospective cohort study

Tuberculosis is the leading cause of morbidity and mortality among children living with the human immunodeficiency virus (HIV), mainly in sub-Saharan Africa, including Ethiopia. Tuberculosis remains a significant health concern for HIV-positive children in Ethiopia. There is a paucity of data on the incidence and predictors of tuberculosis among children living with HIV on antiretroviral therapy in the Wolaita zone. Hence, this study aimed to assess the incidence and predictors of tuberculosis among children living with HIV on antiretroviral therapy in the Wolaita zone between January 2010 to December 2020. A retrospective cohort study was conducted among 389 children receiving antiretroviral therapy in Wolaita zone health facilities between January 2010 to December 2020. The checklist was adapted from the standardized antiretroviral treatment (ART) follow-up form currently used by the institutions’ ART clinics. The Kaplan-Meier survival function and Log-rank were used to estimate the survival for each categorical variable to compare the survival between different exposure groups. Both bivariable and multivariable parametric survival Gompertz models were fitted to identify predictors of tuberculosis among HIV-positive children. The association was summarized using an adjusted hazard ratio (AHR), and statistical significance was declared at 95% CI and p-value < 0.05. The goodness of the model fit was assessed using a Cox-Snell residual plot. The incidence rate of tuberculosis among children living with HIV was 3.5 (95% CI 2.7–4.5) per 100 child years. World Health Organization clinical stage III or IV (AHR = 2.31, 95% CI [1.26, 4.22]), hemoglobin level <10 g/dL (AHR = 2.87, 95% CI [1.51, 5.45]), fair or poor ART adherence (AHR = 4.4, 95% CI[2.18, 9.05]), underweight (AHR = 2.55, 95% CI [1.45, 4.51]), age >10 years (AHR = 3.62; 95% CI [1.29, 10.0]), and cotrimoxazole preventive therapy (AHR = 0.23; 95% CI [0.08, 0.60]) were among the independent predictors of TB occurrence. The incidence of tuberculosis among children on ART was high. HIV-positive children presenting with advanced disease staging (III and IV), anemia, “fair” and “poor” ART adherence, underweight, age above ten years, and not receiving cotrimoxazole preventive therapy were at higher risk of TB. Therefore, counseling on ART adherence, early diagnosis, and prompt treatment of anemia and malnutrition are recommended to avert tuberculosis.

60 APPLIED LIFE SCIENCES↗

The Helix-Loop-Helix motif of human EIF3A regulates translation of proliferative cellular mRNAs

Improper regulation of translation initiation, a vital checkpoint of protein synthesis in the cell, has been linked to a number of cancers. Overexpression of protein subunits of eukaryotic translation initiation factor 3 (eIF3) is associated with increased translation of mRNAs involved in cell proliferation. In addition to playing a major role in general translation initiation by serving as a scaffold for the assembly of translation initiation complexes, eIF3 regulates translation of specific cellular mRNAs and viral RNAs. Mutations in the N-terminal Helix-Loop-Helix (HLH) RNA-binding motif of the EIF3A subunit interfere with Hepatitis C Virus Internal Ribosome Entry Site (IRES) mediated translation initiation in vitro . Here we show that the EIF3A HLH motif controls translation of a small set of cellular transcripts enriched in oncogenic mRNAs, including MYC . We demonstrate that the HLH motif of EIF3A acts specifically on the 5' UTR of MYC mRNA and modulates the function of EIF4A1 on select transcripts during translation initiation. In Ramos lymphoma cell lines, which are dependent on MYC overexpression, mutations in the HLH motif greatly reduce MYC expression, impede proliferation and sensitize cells to anti-cancer compounds. These results reveal the potential of the EIF3A HLH motif in eIF3 as a promising chemotherapeutic target.

59 BASIC BIOLOGICAL SCIENCES↗

Pooled PPIseq: Screening the SARS-CoV-2 and human interface with a scalable multiplexed protein-protein interaction assay platform

Protein-Protein Interactions (PPIs) are a key interface between virus and host, and these interactions are important to both viral reprogramming of the host and to host restriction of viral infection. In particular, viral-host PPI networks can be used to further our understanding of the molecular mechanisms of tissue specificity, host range, and virulence. At higher scales, viral-host PPI screening could also be used to screen for small-molecule antivirals that interfere with essential viral-host interactions, or to explore how the PPI networks between interacting viral and host genomes co-evolve. Current high-throughput PPI assays have screened entire viral-host PPI networks. However, these studies are time consuming, often require specialized equipment, and are difficult to further scale. Here, we develop methods that make larger-scale viral-host PPI screening more accessible. This approach combines the mDHFR split-tag reporter with the iSeq2 interaction-barcoding system to permit massively-multiplexed PPI quantification by simple pooled engineering of barcoded constructs, integration of these constructs into budding yeast, and fitness measurements by pooled cell competitions and barcode-sequencing. We applied this method to screen for PPIs between SARS-CoV-2 proteins and human proteins, screening in triplicate >180,000 ORF-ORF combinations represented by >1,000,000 barcoded lineages. Our results complement previous screens by identifying 74 putative PPIs, including interactions between ORF7A with the taste receptors TAS2R41 and TAS2R7, and between NSP4 with the transmembrane KDELR2 and KDELR3. We show that this PPI screening method is highly scalable, enabling larger studies aimed at generating a broad understanding of how viral effector proteins converge on cellular targets to effect replication.

60 APPLIED LIFE SCIENCES↗

A natural mutation between SARS-CoV-2 and SARS-CoV determines neutralization by a cross-reactive antibody

Epitopes that are conserved among SARS-like coronaviruses are attractive targets for design of cross-reactive vaccines and therapeutics. CR3022 is a SARS-CoV neutralizing antibody to a highly conserved epitope on the receptor binding domain (RBD) on the spike protein that is able to cross-react with SARS-CoV-2, but with lower affinity. Using x-ray crystallography, mutagenesis, and binding experiments, we illustrate that of four amino acid differences in the CR3022 epitope between SARS-CoV-2 and SARS-CoV, a single mutation P384A fully determines the affinity difference. CR3022 does not neutralize SARS-CoV-2, but the increased affinity to SARS-CoV-2 P384A mutant now enables neutralization with a similar potency to SARS-CoV. We further investigated CR3022 interaction with the SARS-CoV spike protein by negative-stain EM and cryo-EM. Three CR3022 Fabs bind per trimer with the RBD observed in different up-conformations due to considerable flexibility of the RBD. In one of these conformations, quaternary interactions are made by CR3022 to the N-terminal domain (NTD) of an adjacent subunit. Overall, this study provides insights into antigenic variation and potential cross-neutralizing epitopes on SARS-like viruses.

59 BASIC BIOLOGICAL SCIENCES↗

Binding of adenovirus species C hexon to prothrombin and the influence of hexon on vector properties in vitro and in vivo

The majority of adenovirus (Ad) vectors are based on human Ad type 5, which is a member of Ad species C. Species C also includes the closely-related types 1, 2, 6, 57 and 89. It is known that coagulation factors bind to Ad5 hexon and play a key role in the liver tropism of Ad5 vectors, but it is unclear how coagulation factors affect vectors derived from other species C Ads. We evaluated species C Ad vectors both in vitro and following intravenous injection in mice. To assess the impact of hexon differences, we constructed chimeric Ad5 vectors that contain the hexon hypervariable regions from other species C types, including vectors with hexon mutations that decreased coagulation factor binding. After intravenous injection into mice, vectors with Ad5 or Ad6 hexon had strong liver tropism, while vectors with chimeric hexon from other Ad types had weaker liver tropism due to inhibition by natural antibodies and complement. In addition, we discovered a novel ability of hexon to bind prothrombin, which is the most abundant coagulation factor in blood, and we found striking differences in the affinity of Ads for human, mouse and bovine coagulation factors. When compared to Ad5, vectors with non-Ad5 species C hexons had considerably higher affinity for both human and mouse prothrombin. Most of the vectors tested were strongly dependent on coagulation factors for liver transduction, but vectors with chimeric Ad6 hexon showed much less dependence on coagulation factors than other vectors. We found that in vitro neutralization experiments with mouse serum predicted in vivo behavior of Ad5 vectors, but in vitro experiments did not predict the in vivo behavior of vectors based on other Ad types. In sum, hexons from different human Ad species C viruses confer diverse properties on vectors, including differing abilities to target the liver.

Tian, Jie↗

Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates

The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses.

60 APPLIED LIFE SCIENCES↗

Immunization of cows with HIV envelope trimers generates broadly neutralizing antibodies to the V2-apex from the ultralong CDRH3 repertoire

The generation of broadly neutralizing antibodies (bnAbs) to conserved epitopes on HIV Envelope (Env) is one of the cornerstones of HIV vaccine research. The animal models commonly used for HIV do not reliably produce a potent broadly neutralizing serum antibody response, with the exception of cows. Cows have previously produced a CD4 binding site response by homologous prime and boosting with a native-like Env trimer. In small animal models, other engineered immunogens were shown to focus antibody responses to the bnAb V2-apex region of Env. Here, we immunized two groups of cows (n = 4) with two regimens of V2-apex focusing Env immunogens to investigate whether antibody responses could be generated to the V2-apex on Env. Group 1 was immunized with chimpanzee simian immunodeficiency virus (SIV)-Env trimer that shares its V2-apex with HIV, followed by immunization with C108, a V2-apex focusing immunogen, and finally boosted with a cross-clade native-like trimer cocktail. Group 2 was immunized with HIV C108 Env trimer followed by the same HIV trimer cocktail as Group 1. Longitudinal serum analysis showed that one cow in each group developed serum neutralizing antibody responses to the V2-apex. Eight and 11 bnAbs were isolated from Group 1 and Group 2 cows, respectively, and showed moderate breadth and potency. Potent and broad responses in this study developed much later than previous cow immunizations that elicited CD4bs bnAbs responses and required several different immunogens. All isolated bnAbs were derived from the ultralong CDRH3 repertoire. The finding that cow antibodies can target more than one broadly neutralizing epitope on the HIV surface reveals the generality of elongated structures for the recognition of highly glycosylated proteins. The exclusive isolation of ultralong CDRH3 bnAbs, despite only comprising a small percent of the cow repertoire, suggests these antibodies outcompete the long and short CDRH3 antibodies during the bnAb response.

Microbiology↗

Understanding early HIV-1 rebound dynamics following antiretroviral therapy interruption: The importance of effector cell expansion

Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and highlights the importance of the effector cell expansion rate. Our results show that post-treatment controllers and non-controllers can be distinguished based on the effector cell expansion rate in our models. Furthermore, these results demonstrate the potential of using dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption.

60 APPLIED LIFE SCIENCES↗

SARS-CoV-2 evolution balances conflicting roles of N protein phosphorylation

All lineages of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, contain mutations between amino acids 199 and 205 in the nucleocapsid (N) protein that are associated with increased infectivity. The effects of these mutations have been difficult to determine because N protein contributes to both viral replication and viral particle assembly during infection. Here, we used single-cycle infection and virus-like particle assays to show that N protein phosphorylation has opposing effects on viral assembly and genome replication. Ancestral SARS-CoV-2 N protein is densely phosphorylated, leading to higher levels of genome replication but 10-fold lower particle assembly compared to evolved variants with low N protein phosphorylation, such as Delta (N:R203M), Iota (N:S202R), and B.1.2 (N:P199L). A new open reading frame encoding a truncated N protein called N*, which occurs in the B.1.1 lineage and subsequent lineages of the Alpha, Gamma, and Omicron variants, supports high levels of both assembly and replication. Our findings help explain the enhanced fitness of viral variants of concern and a potential avenue for continued viral selection.

Microbiology↗

Soft matter and nanomaterials characterization by cryogenic transmission electron microscopy

Soft matter has historically been an unlikely candidate for investigation by electron microscopy techniques due to damage by the electron beam as well as inherent instability under a high vacuum environment. Characterization of soft matter has often relied on ensemble-scattering techniques. The recent development of cryogenic transmission electron microscopy (cryo-TEM) provides the soft matter community with an exciting opportunity to probe the structure of soft materials in real space. Cryo-TEM reduces beam damage and allows for characterization in a native, frozen-hydrated state, providing direct visual representation of soft structure. This article reviews cryo-TEM in soft materials characterization and illustrates how it has provided unique insights not possible by traditional ensemble techniques. Soft matter systems that have benefited from the use of cryo-TEM include biological-based “soft” nanoparticles (e.g., viruses and conjugates), synthetic polymers, supramolecular materials as well as the organic–inorganic interface of colloidal nanoparticles. We conclude that while many challenges remain, such as combining structural and chemical analyses; the opportunity for soft matter research to leverage newly developed cryo-TEM techniques continues to excite.

36 MATERIALS SCIENCE↗

SARS-CoV-2 Cases Reported on International Arriving and Domestic Flights: United States, January 2020–December 2021

Objectives. To describe trends in the number of air travelers categorized as infectious with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2; the virus that causes COVID-19) in the context of total US COVID-19 vaccinations administered, and overall case counts of SARS-CoV-2 in the United States. Methods. We searched the Quarantine Activity Reporting System (QARS) database for travelers with inbound international or domestic air travel, a positive SARS-CoV-2 lab result, and a surveillance categorization of SARS-CoV-2 infection reported during January 2020 to December 2021. Travelers were categorized as infectious during travel if they had arrival dates from 2 days before to 10 days after symptom onset or a positive viral test. Results. We identified 80 715 persons meeting our inclusion criteria; 67 445 persons (83.6%) had at least 1 symptom reported. Of 67 445 symptomatic passengers, 43 884 (65.1%) reported an initial symptom onset date after their flight arrival date. The number of infectious travelers mirrored the overall number of US SARS-CoV-2 cases. Conclusions. Most travelers in the study were asymptomatic during travel, and therefore unknowingly traveled while infectious. During periods of high community transmission, it is important for travelers to stay up to date with COVID-19 vaccinations and consider wearing a high-quality mask to decrease the risk of transmission. (Am J Public Health. 2023;113(8):904–908. https://doi.org/10.2105/AJPH.2023.307325 )

Public, Environmental & Occupational Health↗

HIV Databases video tutorial on use of the HIV sequence quality control tool

The HIV Databases at LANL (https://www.hiv.lanl.gov) provide many tools for HIV data retrieval and analysis. The quality control tool (https://www.hiv.lanl.gov/content/sequence/QC/index.html) is used to check the quality of new HIV sequence data, help the user determine which subtype of virus belongs to, and prepare the data for submission to the database. This video gives a 10 minute overview of the use of the tool and illustrates results form a sample data set.

59 BASIC BIOLOGICAL SCIENCES↗